Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
The estimation of EEG generating sources constitutes an Inverse Problem (IP) in Neuroscience. This is an ill-posed problem due to the non-uniqueness of the solution and regularization or prior information is needed to undertake Electrophysiology Source Imaging. Structured Sparsity priors can be attained through combinations of (L1 norm-based) and (L2 norm-based) constraints such as the Elastic Net (ENET) and Elitist Lasso (ELASSO) models. The former model is used to find solutions with a small number of smooth nonzero patches, while the latter imposes different degrees of sparsity simultaneously along different dimensions of the spatio-temporal matrix solutions. Both models have been addressed within the penalized regression approach, where the regularization parameters are selected heuristically, leading usually to non-optimal and computationally expensive solutions. The existing Bayesian formulation of ENET allows hyperparameter learning, but using the computationally intensive Monte Carlo/Expectation Maximization methods, which makes impractical its application to the EEG IP. While the ELASSO have not been considered before into the Bayesian context. In this work, we attempt to solve the EEG IP using a Bayesian framework for ENET and ELASSO models. We propose a Structured Sparse Bayesian Learning algorithm based on combining the Empirical Bayes and the iterative coordinate descent procedures to estimate both the parameters and hyperparameters. Using realistic simulations and avoiding the inverse crime we illustrate that our methods are able to recover complicated source setups more accurately and with a more robust estimation of the hyperparameters and behavior under different sparsity scenarios than classical LORETA, ENET and LASSO Fusion solutions. We also solve the EEG IP using data from a visual attention experiment, finding more interpretable neurophysiological patterns with our methods. The Matlab codes used in this work, including Simulations, Methods, Quality Measures and Visualization Routines are freely available in a public website.
We have identified an electroencephalographic (EEG) based statistical classifier that correctly distinguishes children with histories of Protein Energy Malnutrition (PEM) in the first year of life from healthy controls with 0.82% accuracy (area under the ROC curve). Our previous study achieved similar accuracy but was based on scalp quantitative EEG features that precluded anatomical interpretation. We have now employed BC-VARETA, a novel high-resolution EEG source imaging method with minimal leakage and maximal sparseness, which allowed us to identify a classifier in the source space. The EEGs were recorded in 1978 in a sample of 108 children who were 5–11 years old and were participants in the 45+ year longitudinal Barbados Nutrition Study. The PEM cohort experienced moderate-severe PEM limited to the first year of life and were age, handedness and gender-matched with healthy classmates who served as controls. In the current study, we utilized a machine learning approach based on the elastic net to create a stable sparse classifier. Interestingly, the classifier was driven predominantly by nutrition group differences in alpha activity in the lingual gyrus. This structure is part of the pathway associated with generating alpha rhythms that increase with normal maturation. Our findings indicate that the PEM group showed a significant decrease in alpha activity, suggestive of a delay in brain development. Childhood malnutrition is still a serious worldwide public health problem and its consequences are particularly severe when present during early life. Deficits during this critical period are permanent and predict impaired cognitive and behavioral functioning later in life. Our EEG source classifier may provide a functionally interpretable diagnostic technology to study the effects of early childhood malnutrition on the brain, and may have far-reaching applicability in low resource settings.
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